Molecular biomedicine最新文献

Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases.

IF 6.3

Molecular biomedicine Pub Date : 2025-03-22 DOI: 10.1186/s43556-025-00253-y

Aditya Dipakrao Hajare, Neha Dagar, Anil Bhanudas Gaikwad

{"title":"Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases.","authors":"Aditya Dipakrao Hajare, Neha Dagar, Anil Bhanudas Gaikwad","doi":"10.1186/s43556-025-00253-y","DOIUrl":"10.1186/s43556-025-00253-y","url":null,"abstract":"Klotho, initially introduced as an anti-aging protein, is expressed in the brain, pancreas, and most prominently in the kidney. The two forms of Klotho (membrane-bound and soluble form) have diverse pharmacological functions such as anti-inflammatory, anti-oxidative, anti-fibrotic, tumour-suppressive etc. The membrane-bound form plays a pivotal role in maintaining kidney homeostasis by regulating fibroblast growth factor 23 (FGF 23) signalling, vitamin D metabolism and phosphate balance. Klotho deficiency has been linked with significantly reduced protection against various kidney pathological phenotypes, including diabetic kidney disease (DKD), which is a major cause of chronic kidney disease leading to end-stage kidney disease. Owing to the pleiotropic actions of klotho, it has shown beneficial effects in DKD by tackling the complex pathophysiology and reducing kidney inflammation, oxidative stress, as well as fibrosis. Moreover, the protective effect of klotho extends beyond DKD in other pathological conditions, including cardiovascular diseases, alzheimer's disease, cancer, inflammatory bowel disease, and liver disease. Therefore, this review summarizes the relationship between Klotho expression and various diseases with a special emphasis on DKD, the distinct mechanisms and the potential of exogenous Klotho supplementation as a therapeutic strategy. Future research into exogenous Klotho could unravel novel treatment avenues for DKD and other diseases.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"19"},"PeriodicalIF":6.3,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Liquid biopsies in cancer.

IF 6.3

Molecular biomedicine Pub Date : 2025-03-20 DOI: 10.1186/s43556-025-00257-8

Hang Yin, Manjie Zhang, Yu Zhang, Xuebing Zhang, Xia Zhang, Bin Zhang

{"title":"Liquid biopsies in cancer.","authors":"Hang Yin, Manjie Zhang, Yu Zhang, Xuebing Zhang, Xia Zhang, Bin Zhang","doi":"10.1186/s43556-025-00257-8","DOIUrl":"10.1186/s43556-025-00257-8","url":null,"abstract":"Cancer ranks among the most lethal diseases worldwide. Tissue biopsy is currently the primary method for the diagnosis and biological analysis of various solid tumors. However, this method has some disadvantages related to insufficient tissue specimen collection and intratumoral heterogeneity. Liquid biopsy is a noninvasive approach for identifying cancer-related biomarkers in peripheral blood, which allows for repetitive sampling across multiple time points. In the field of liquid biopsy, representative biomarkers include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes. Many studies have evaluated the prognostic and predictive roles of CTCs and ctDNA in various solid tumors. Although these studies have limitations, the results of most studies appear to consistently demonstrate the correlations of high CTC counts and ctDNA mutations with lower survival rates in cancer patients. Similarly, a reduction in CTC counts throughout therapy may be a potential prognostic indicator related to treatment response in advanced cancer patients. Moreover, the biochemical characteristics of CTCs and ctDNA can provide information about tumor biology as well as resistance mechanisms against targeted therapy. This review discusses the current clinical applications of liquid biopsy in cancer patients, emphasizing its possible utility in outcome prediction and treatment decision-making.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"18"},"PeriodicalIF":6.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

M6A-modified BFSP1 induces aerobic glycolysis to promote liver cancer growth and metastasis through upregulating tropomodulin 4.

IF 6.3

Molecular biomedicine Pub Date : 2025-03-18 DOI: 10.1186/s43556-025-00256-9

Rong Li, Shunle Li, Lin Shen, Junhui Li, Di Zhang, Jinmin Yu, Lanxuan Huang, Na Liu, Hongwei Lu, Meng Xu

{"title":"M6A-modified BFSP1 induces aerobic glycolysis to promote liver cancer growth and metastasis through upregulating tropomodulin 4.","authors":"Rong Li, Shunle Li, Lin Shen, Junhui Li, Di Zhang, Jinmin Yu, Lanxuan Huang, Na Liu, Hongwei Lu, Meng Xu","doi":"10.1186/s43556-025-00256-9","DOIUrl":"10.1186/s43556-025-00256-9","url":null,"abstract":"RNA N6-methyladenosine (m6A) is a common RNA modification in eukaryotes, and its abnormal regulation is closely related to cancer progression. Aerobic glycolysis is a main way for cancer cells to obtain energy. It was found that beaded filament structural protein 1 (BFSP1) is a m6A related gene in liver cancer. However, the effect of m6A-modified BFSP1 on aerobic glycolysis and how it is regulated in liver cancer progression have not been explored. Here, we found that BFSP1 was upregulated in liver cancer cells and tissues. Overexpression of BFSP1 promoted the viability, invasion, and aerobic glycolysis of liver cancer cells, whereas knockdown of BFSP1 showed the opposite effects. Co-immunoprecipitation, immunofluorescence and GST pull down analyses showed that BFSP1 directly interacted with tropomodalin 4 (TMOD4), and knockdown of TMOD4 reversed BFSP1 overexpression-induced malignant phenotypes and aerobic glycolysis in liver cancer cells. Moreover, methyltransferase-like 3 (METTL3) enhanced BFSP1 stability by augmenting m6A modification of BFSP1 mRNA, which is achieved in a YTHDF1-dependent manner. In vivo experiments in mice confirmed that METTL3 increased BFSP1 stability by promoting m6A modification of BFSP1 mRNA, and knockdown of BFSP1 inhibited tumor growth and metastasis. In summary, METTL3-mediated m6A methylation of BFSP1 mRNA plays an important role in the aerobic glycolysis and progression of liver cancer, providing a potential therapeutic strategy for liver cancer.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"17"},"PeriodicalIF":6.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel neuroprotective mechanism of selegiline by suppressing the pro-apoptotic activity of protein disulfide isomerase.

IF 6.3

Molecular biomedicine Pub Date : 2025-03-17 DOI: 10.1186/s43556-025-00255-w

Yuting Xie, Bing Chen, Piao Luo, Jingnan Huang, Jigang Wang, Jichao Sun, Zhen Liang

引用次数: 0

Correction: A promising mRNA vaccine derived from the JN.1 spike protein confers protective immunity against multiple emerged Omicron variants.

IF 6.3

Molecular biomedicine Pub Date : 2025-03-17 DOI: 10.1186/s43556-025-00260-z

Danyi Ao, Dandan Peng, Cai He, Chunjun Ye, Weiqi Hong, Xiya Huang, Yishan Lu, Jie Shi, Yu Zhang, Jian Liu, Xiawei Wei, Yuquan Wei

引用次数: 0

Regulation of histone H3K27 methylation in inflammation and cancer.

IF 6.3

Molecular biomedicine Pub Date : 2025-03-05 DOI: 10.1186/s43556-025-00254-x

Jing Ma, Yalin Zhang, Jingyuan Li, Yanqi Dang, Dan Hu

{"title":"Regulation of histone H3K27 methylation in inflammation and cancer.","authors":"Jing Ma, Yalin Zhang, Jingyuan Li, Yanqi Dang, Dan Hu","doi":"10.1186/s43556-025-00254-x","DOIUrl":"10.1186/s43556-025-00254-x","url":null,"abstract":"Inflammation is a multifaceted defense mechanism of the immune system against infection. Chronic inflammation is intricately linked to all stages of tumorigenesis and is therefore associated with an elevated risk of developing serious cancers. Epigenetic mechanisms have the capacity to trigger inflammation as well as facilitate tumor development and transformation within an inflammatory context. They achieve this by dynamically modulating the expression of both pro-inflammatory and anti-inflammatory cytokines, which in turn sustains chronic inflammation. The aberrant epigenetic landscape reconfigures the transcriptional programs of inflammatory and oncogenic genes. This reconfiguration is pivotal in dictating the biological functions of both tumor cells and immune cells. Aberrant histone H3 lysine 27 site (H3K27) methylation has been shown to be involved in biological behaviors such as inflammation development, tumor progression, and immune response. The establishment and maintenance of this repressive epigenetic mark is dependent on the involvement of the responsible histone modifying enzymes enhancer of zeste homologue 2 (EZH2), jumonji domain containing 3 (JMJD3) and ubiquitously transcribed tetratricopeptide repeat gene X (UTX) as well as multiple cofactors. In addition, specific pharmacological agents have been shown to modulate H3K27 methylation levels, thereby modulating inflammation and carcinogenesis. This review comprehensively summarises the current characteristics and clinical significance of epigenetic regulation of H3K27 methylation in the context of inflammatory response and tumor progression.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"14"},"PeriodicalIF":6.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A promising mRNA vaccine derived from the JN.1 spike protein confers protective immunity against multiple emerged Omicron variants.

IF 6.3

Molecular biomedicine Pub Date : 2025-03-04 DOI: 10.1186/s43556-025-00258-7

Danyi Ao, Dandan Peng, Cai He, Chunjun Ye, Weiqi Hong, Xiya Huang, Yishan Lu, Jie Shi, Yu Zhang, Jian Liu, Xiawei Wei, Yuquan Wei

{"title":"A promising mRNA vaccine derived from the JN.1 spike protein confers protective immunity against multiple emerged Omicron variants.","authors":"Danyi Ao, Dandan Peng, Cai He, Chunjun Ye, Weiqi Hong, Xiya Huang, Yishan Lu, Jie Shi, Yu Zhang, Jian Liu, Xiawei Wei, Yuquan Wei","doi":"10.1186/s43556-025-00258-7","DOIUrl":"10.1186/s43556-025-00258-7","url":null,"abstract":"Despite the declared end of the COVID-19 pandemic, SARS-CoV-2 continues to evolve, with emerging JN.1-derived subvariants (e.g., KP.2, KP.3) compromising the efficacy of current XBB.1.5-based vaccines. To address this, we developed an mRNA vaccine encoding the full-length spike protein of JN.1, incorporating GSAS and 2P mutations and encapsulated in lipid nanoparticles (LNPs). The JN.1-mRNA vaccine elicited robust humoral and cellular immune responses in mice, including high JN.1-specific IgG titers, cross-neutralizing antibodies, and increased T follicular helper (Tfh) cells, germinal center (GC) B cells, and T cell cytokines. Importantly, immunity persisted for up to six months and induced RBD-specific long-lived plasma cells. We also compared the immune responses induced by homologous and heterologous vaccination regimens, and our results demonstrated that the heterologous regimen-combining JN.1-mRNA with a recombinant protein vaccine (RBDJN.1-HR)-induced stronger responses. These findings highlight the JN.1-mRNA vaccine constitutes an effective prophylactic approach against JN.1-related variants, as it induces potent neutralizing antibody responses across all tested lineages. This enhanced immunogenicity is expected to significantly reduce hospitalization rates and mitigate post-COVID complications associated with JN.1 and KP.3 infections. This study emphasizes the need for timely vaccine updates and the adaptability of mRNA vaccines in addressing emerging pathogens, providing a framework for combating future infectious diseases. Collectively, these results offer critical insights for vaccine design and public health strategies in response to emerging SARS-CoV-2 variants.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"13"},"PeriodicalIF":6.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GSDMD-mediated pyroptosis: molecular mechanisms, diseases and therapeutic targets.

IF 6.3

Molecular biomedicine Pub Date : 2025-02-25 DOI: 10.1186/s43556-025-00249-8

Yujuan Li, Bin Guo

{"title":"GSDMD-mediated pyroptosis: molecular mechanisms, diseases and therapeutic targets.","authors":"Yujuan Li, Bin Guo","doi":"10.1186/s43556-025-00249-8","DOIUrl":"10.1186/s43556-025-00249-8","url":null,"abstract":"Pyroptosis is a regulated form of inflammatory cell death in which Gasdermin D (GSDMD) plays a central role as the key effector molecule. GSDMD-mediated pyroptosis is characterized by complex biological features and considerable heterogeneity in its expression, mechanisms, and functional outcomes across various tissues, cell types, and pathological microenvironments. This heterogeneity is particularly pronounced in inflammation-related diseases and tumors. In the context of inflammatory diseases, GSDMD expression is typically upregulated, and its activation in macrophages, neutrophils, T cells, epithelial cells, and mitochondria triggers both pyroptotic and non-pyroptotic pathways, leading to the release of pro-inflammatory cytokines and exacerbation of tissue damage. However, under certain conditions, GSDMD-mediated pyroptosis may also serve a protective immune function. The expression of GSDMD in tumors is regulated in a more complex manner, where it can either promote immune evasion or, in some instances, induce tumor cell death. As our understanding of GSDMD's role continues to progress, there have been advancements in the development of inhibitors targeting GSDMD-mediated pyroptosis; however, these therapeutic interventions remain in the preclinical phase. This review systematically examines the cellular and molecular complexities of GSDMD-mediated pyroptosis, with a particular emphasis on its roles in inflammation-related diseases and cancer. Furthermore, it underscores the substantial therapeutic potential of GSDMD as a target for precision medicine, highlighting its promising clinical applications.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"11"},"PeriodicalIF":6.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cancer brain metastasis: molecular mechanisms and therapeutic strategies.

IF 6.3

Molecular biomedicine Pub Date : 2025-02-25 DOI: 10.1186/s43556-025-00251-0

Yu Lu, Yunhang Huang, Chenyan Zhu, Zhidan Li, Bin Zhang, Hui Sheng, Haotai Li, Xixi Liu, Zhongwen Xu, Yi Wen, Jing Zhang, Liguo Zhang

{"title":"Cancer brain metastasis: molecular mechanisms and therapeutic strategies.","authors":"Yu Lu, Yunhang Huang, Chenyan Zhu, Zhidan Li, Bin Zhang, Hui Sheng, Haotai Li, Xixi Liu, Zhongwen Xu, Yi Wen, Jing Zhang, Liguo Zhang","doi":"10.1186/s43556-025-00251-0","DOIUrl":"10.1186/s43556-025-00251-0","url":null,"abstract":"Brain metastases (BMs) are the most common intracranial tumors in adults and the major cause of cancer-related morbidity and mortality. The occurrence of BMs varies according to the type of primary tumors with most frequence in lung cancer, melanoma and breast cancer. Among of them, lung cancer has been reported to have a higher risk of BMs than other types of cancers with 40 ~ 50% of such patients will develop BMs during the course of disease. BMs lead to many neurological complications and result in a poor quality of life and short life span. Although the treatment strategies were improved for brain tumors in the past decades, the prognosis of BMs patients is grim. Poorly understanding of the molecular and cellular characteristics of BMs and the complicated interaction with brain microenvironment are the major reasons for the dismal prognosis of BM patients. Recent studies have enhanced understanding of the mechanisms of BMs. The newly identified potential therapeutic targets and the advanced therapeutic strategies have brought light for a better cure of BMs. In this review, we summarized the mechanisms of BMs during the metastatic course, the molecular and cellular landscapes of BMs, and the advances of novel drug delivery systems for overcoming the obstruction of blood-brain barrier (BBB). We further discussed the challenges of the emerging therapeutic strategies, such as synergistic approach of combining targeted therapy with immunotherapy, which will provide vital clues for realizing the precise and personalized medicine for BM patients in the future.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"12"},"PeriodicalIF":6.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

G protein-coupled receptor 107 deficiency promotes development of diabetic nephropathy.

IF 6.3

Molecular biomedicine Pub Date : 2025-02-11 DOI: 10.1186/s43556-025-00250-1

Deping Xu, Ziwen Tong, Ping Yang, Qiong Chen, Suhua Wang, Wei Zhao, Linzi Han, Yu Yin, Ruyue Xu, Min Zhang, Chunlin Cai, Deguang Wang, Dandan Zang, Guoling Zhou, Haisheng Zhou

{"title":"G protein-coupled receptor 107 deficiency promotes development of diabetic nephropathy.","authors":"Deping Xu, Ziwen Tong, Ping Yang, Qiong Chen, Suhua Wang, Wei Zhao, Linzi Han, Yu Yin, Ruyue Xu, Min Zhang, Chunlin Cai, Deguang Wang, Dandan Zang, Guoling Zhou, Haisheng Zhou","doi":"10.1186/s43556-025-00250-1","DOIUrl":"10.1186/s43556-025-00250-1","url":null,"abstract":"Diabetic nephropathy (DN) is characterized by glomerular basement membrane (GBM) thickening, primarily due to the abnormal accumulation of collagen type IV (COL4) in the extracellular matrix (ECM) of podocytes. Podocytes endocytosis is crucial for maintaining COL4 balance and GBM integrity. Previous studies have shown that G protein-coupled receptor 107 (GPR107) facilitates clathrin-dependent transferrin internalization and recycling in murine embryonic fibroblast cells. Therefore, the aim of the study is to investigate the role of GPR107 in regulating COL4 balance within the podocytes ECM and its potential as a therapeutic target for DN. Here, we found a significant decrease in GPR107 expression in renal tissues from DN patients and streptozocin (STZ)-induced DN mice. Furthermore, GPR107-deficient mice with STZ-induced DN exhibited more severe kidney damage, marked by increased GBM thickening and COL4 accumulation. In vitro, GPR107 deficiency under high-glucose conditions promoted COL4 accumulation in the ECM of podocytes due to increased COL4 production and decreased COL4 degradation. Mechanistically, we demonstrated that GPR107 contributes to angiotensin II receptor type 1 (AT1R) internalization through clathrin-mediated endocytosis (CME) in podocytes. Therefore, GPR107 deficiency impairs AT1R internalization, leading to increased membrane-bound AT1R. This, in turn, activates the AT1R/Ca2+ signaling pathway to promote phosphorylation of cAMP-response element-binding protein (CREB), ultimately enhancing COL4 synthesis and inhibiting the expression of matrix metalloproteinase 2 (MMP-2). These findings shed light on new functions of GPR107 in DN and offer new insights into a therapeutic target for DN.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"10"},"PeriodicalIF":6.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0